The multifaceted nature and swift progression of Amyotrophic Lateral Sclerosis (ALS) pose considerable challenges to our understanding of its evolution and interplay with comorbid conditions. This study seeks to elucidate the temporal dynamics of ALS progression and its interaction with associated diseases. We employed a principal tree-based model to decipher patterns within clinical data derived from a population-based database in Taiwan. The disease progression was portrayed as branched trajectories, each path representing a series of distinct stages. Each stage embodied the cumulative occurrence of co-existing diseases, depicted as nodes on the tree, with edges symbolizing potential transitions between these linked nodes. Our model identified eight distinct ALS patient trajectories, unveiling unique patterns of disease associations at various stages of progression. These patterns may suggest underlying disease mechanisms or risk factors. This research re-conceptualizes ALS progression as a migration through diverse stages, instead of the perspective of a sequence of isolated events. This new approach illuminates patterns of disease association across different progression phases. The insights obtained from this study hold the potential to inform doctors regarding the development of personalized treatment strategies, ultimately enhancing patient prognosis and quality of life.

Download full-text PDF

Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC10604752PMC
http://dx.doi.org/10.3390/biomedicines11102629DOI Listing

Publication Analysis

Top Keywords

amyotrophic lateral
8
lateral sclerosis
8
sclerosis als
8
als progression
8
patterns disease
8
progression
6
als
5
detection amyotrophic
4
als comorbidity
4
comorbidity trajectories
4

Similar Publications

Amyotrophic lateral sclerosis (ALS) is a severe disease of the central nervous system (CNS) characterized by motor neuron damage leading to death from respiratory failure. The neurodegenerative process in ALS is characterized by an accumulation of aberrant proteins (TDP-43, SOD1, etc.) in CNS cells.

View Article and Find Full Text PDF

Motor neuron diseases are not exclusively motor; the SSR paradigm.

Amyotroph Lateral Scler Frontotemporal Degener

January 2025

2nd Second Department of Neurology, National and Kapodistrian University of Athens, School of Medicine, Attikon University Hospital, Athens, Greece.

Motor Neuron Diseases (MNDs), familial and sporadic, are progressive neurodegenerative disorders that, for an extended period in the past, were considered purely motor disorders. During the course of the disease, however, some patients exhibit concomitant non-motor signs; thus, MNDs are currently perceived as multisystem disorders. Assessment of non-motor symptoms is usually performed clinically, although laboratory tests can also be routinely used to objectively evaluate these symptoms.

View Article and Find Full Text PDF

Superoxide dismutase 1 (SOD1) aggregation is implicated in the development of Amyotrophic Lateral Sclerosis (ALS). Despite knowledge of the role of SOD1 aggregation, the mechanistic understanding remains elusive. Our investigation aimed to unravel the complex steps involved in SOD1 aggregation associated with ALS.

View Article and Find Full Text PDF

TDP-43 nuclear retention is antagonized by hypo-phosphorylation of its C-terminus in the cytoplasm.

Commun Biol

January 2025

Université Paris-Saclay, INSERM U1204, Univ Evry, Structure-Activité des Biomolécules Normales et Pathologiques (SABNP), Evry-Courcouronnes, France.

Protein aggregation is a hallmark of many neurodegenerative disorders, including amyotrophic lateral sclerosis (ALS), in which TDP-43, a nuclear RNA-binding protein, forms cytoplasmic inclusions. Here, we have developed a robust and automated method to assess protein self-assembly in the cytoplasm using microtubules as nanoplatforms. Importantly, we have analyzed specifically the self-assembly of full-length TDP-43 and its mRNA binding that are regulated by the phosphorylation of its self-adhesive C-terminus, which is the recipient of many pathological mutations.

View Article and Find Full Text PDF

Structural insights into the role of reduced cysteine residues in SOD1 amyloid filament formation.

Proc Natl Acad Sci U S A

February 2025

Department of Agricultural Biotechnology, and Research Institute of Agriculture and Life Sciences, CALS, Seoul National University, Seoul 08826, Republic of Korea.

The formation of superoxide dismutase 1 (SOD1) filaments has been implicated in amyotrophic lateral sclerosis (ALS). Although the disulfide bond formed between Cys57 and Cys146 in the active state has been well studied, the role of the reduced cysteine residues, Cys6 and Cys111, in SOD1 filament formation remains unclear. In this study, we investigated the role of reduced cysteine residues by determining and comparing cryoelectron microscopy (cryo-EM) structures of wild-type (WT) and C6A/C111A SOD1 filaments under thiol-based reducing and metal-depriving conditions, starting with protein samples possessing enzymatic activity.

View Article and Find Full Text PDF

Want AI Summaries of new PubMed Abstracts delivered to your In-box?

Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!